The correlation of homologous recombination deficiency status with and Olaparib efficacy in Chinese ovarian cancer patients.

Abstract

e17556 Background: Homologous recombination and DNA repair are important for genome maintenance. Genetic variations in essential homologous recombination genes, including BRCA1 and BRCA2, results in homologous recombination deficiency (HRD) can be a target for therapeutic strategies of ovarian cancer (OC) including poly (ADP-ribose) polymerase inhibitors (PARPi). Here, we proposed an emerging method based on ADx-GSS algorithm to predict HRD status and explore the correlation between HRD status and first-line maintenance therapy of Olaparib in OC patients or Olaparib maintenance therapy in platinum-sensitive relapsed (PSR) OC patients. Methods: Formalin-fixed, paraffin-embedded tissues of 38 consented OC patients between January 2016 and March 2021 were retrospectively collected. Genomic DNA was extracted and subjected to AmoyDx HRD Focus Panel (Amoy Diagnostics Co., Ltd) covering HRD score and BRCA1/2. The HRD score was calculated as the weighted sum of different types of copy number variation (CNV) trained through BRCAness events. Tumors were defined as genomic instability with an HRD score of ≥ 50 (i.e. HRD-positive). The primary endpoint was progression-free survival (PFS), and was assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: Histology of collected samples were mostly serous OC (84.2%). All samples were at stage III-IV (80.84%). The fractions of HRD-positive (n = 26) and HRD-negative (n = 12) group were 68.4%, and 31.6%, respectively. 65.8% (n = 25) of the OC patients had received Olaparib first-line maintenance therapy and 34.2% (n = 13) of PSR patients had received Olaparib maintenance therapy. In December 2021, 34.2% (n = 13) of the whole patients had relapsed. A significant PFS benefit was seen in HRD-positive patients compared with HRD-negative ones (P = 0.0017) or in the first-line maintenance treated population (P = 0.0068). In patients with HRD-positive tumors that did not have BRCA mutations, the PFS benefit was improved versus HRD-negative patients without BRCA mutations. However, Olaparib showed no efficacy difference between HRD-positive and HRD-negative tumor in PSR OC patients. Conclusions: HRD status tested by AmoyDx HRD Focus Panel is significantly correlated with the efficacy of Olaparib, and our results demonstrated a significant PFS benefit for HRD-positive patients compared with HRD-negative patients, especially for patients received Olaparib first-line maintenance therapy.